Methods and devices for treating skin conditions

ABSTRACT

Provided are methods and devices for treating skin conditions using an electrical signal applied to the skin of a subject.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of International ApplicationSerial No. PCT/US2021/058329, filed Nov. 5, 2021, which claims thebenefit of U.S. Provisional Patent Application No. 63/110,290, filed onNov. 5, 2020, the entirety of which is incorporated herein by reference.

BACKGROUND

Chronic conditions of the eye, such as blepharitis and dry eye, haveconfounded medicine's best efforts at treatment for a very long time.The etiology of many chronic conditions of the eye, such as blepharitisand dry eye, has been thought to comprise several causes and that such aplurality of causes was the reason an effective treatment has eludedpractitioners. Bacteria are thought to play a major causative role invarious chronic conditions, including blepharitis and dry eye.

Biofilms, which can comprise an extracellular matrix of proteins andpolysaccharides, are important for the survival of bacteria in nature,as bacteria do not survive well outside of such microenvironments. It isthought that biofilms may contribute to the establishment andprogression of certain chronic diseases, such as gingivitis, earinfections, gastrointestinal ulcers, urinary tract infections, and evensome pulmonary infections. However, as the biofilm builds on a surface,it can become highly resistant to traditional treatments of bacteria,such as the use of antibiotics.

Blepharitis, which can comprise inflammation of the eyelid is a seriousand very common (e.g., in older patients) condition that may eventuallyleads to destruction of the tear glands, potentially resulting in dryeye disease. In view of poor results observed in antibiotic treatment ofbacteria in biofilms, new methods of treating chronic conditionsblepharitis and its causes are needed.

SUMMARY

Provided herein are embodiments of a device for providing an electricaltherapy to a skin of a subject comprising: a transmission surfacecomprising a first electrode and a second electrode; a power supply inelectrical communication with the first and second electrodes; acontroller to regulate voltage, current, or a combination thereof of anelectrical signal supplied the first and second electrodes the first andsecond electrodes by the power supply.

In some embodiments, the controller supplies a first voltage to thefirst electrode, and a second voltage to the second electrode, therebycreating a voltage potential between the first electrode and the secondelectrode. In some embodiments, the first and second electrode contact askin surface to generate an electric current across through the skin. Insome embodiments, said first voltage and second voltage are selected tovaporize a bio-film.

In some embodiments, the device further comprises a feedback loop tomeasure an impedance of the skin, and wherein the controller regulatesthe electrical signal based on a measured impedance.

In some embodiments, the voltage of the electrical signal is about 0.1to 20 volts (V). In some embodiments, the current of the electricalsignal is less than about 5 milliamps (mA).

In some embodiments, the device further comprises an enclosure to housethe power supply and the controller, wherein a wire lead extends fromthe enclosure to the transmission surface. In some embodiments, thecurrent of the electrical signal is an alternating current. In someembodiments, the current of the electrical signal is a direct current.

In some embodiments, the electrical therapy is used to treat acne,snoring, dry eye, premature aging, or a combination thereof.

Provided herein are embodiments of a method of applying an electricaltherapy on a skin of a subject, the method comprising: contacting a skinsurface with a first electrode and a second electrode; generating anelectrical current through the skin by supplying a first voltage to thefirst electrode and a second voltage to the second electrode, whereinthe first voltage is different than the second voltage.

In some embodiments, the electrical current is less than about 5milliamps. In some embodiments, the first voltage and the second voltageare about 0.1 to 20 volts (V). In some embodiments, the method furthercomprises applying a solution to the skin surface to reduce electricalresistivity of the skin.

In some embodiments, the electrical therapy is an acne reductiontherapy. In some embodiments, the acne reduction therapy reducesinstances of Acne Rosacea inflammation.

In some embodiments, the generation of the electrical current vaporizesa biofilm. In some embodiments, the electrical therapy treats a snoringcondition. In some embodiments, the skin surface is proximal to a nasalcavity. In some embodiments, the first and second electrodes areprovided on a transmission surface, and wherein said transmissionsurface comprises a curvature adapted to conform to a bridge of a nose.In some embodiments, the first and second electrodes are provided on atransmission surface.

In some embodiments, the electrical therapy treats a premature agingcondition. In some embodiments, the electrical therapy treats a dry eyecondition.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1A depicts a schematic of a system for applying electric energy toa target area of a subject, according to some embodiments herein.

FIG. 1B depicts a schematic of a system for applying electric energy toa target area of a subject, according to some embodiments herein.

FIG. 2A depicts a system for applying electric energy to a target areaof a subject, according to some embodiments herein.

FIG. 2B depicts a system for applying electric energy to a target areaof a subject, according to some embodiments herein.

FIGS. 3A, 3B, 3C, 3D and 3E depict components of systems and devicesuseful for applying electric energy to a target area of a subject,according to some embodiments herein.

FIG. 4 depicts an example of a twin peak monophasic waveform, inaccordance with embodiments of devices, systems, and methods describedherein.

FIG. 5 depicts an example of a biphasic asymmetrical waveform, inaccordance with embodiments of devices, systems, and methods describedherein.

FIG. 6 depicts an example of an unbalanced triphasic waveform, inaccordance with embodiments of devices, systems, and methods describedherein.

FIG. 7 is a schematic representation of a controller, in accordance withembodiments of devices, systems, and methods described herein.

DETAILED DESCRIPTION

Disclosed herein are novel systems, devices, and methods useful fortreatment of conditions of the skin and eyes. For example, systems,devices, and methods described herein can be used to treat or preventskin conditions (e.g., diseases) caused by or associated with thepresence of bacteria and/or the presence of biofilms in or around atarget area of a subject, such as a skin surface (e.g., a skin surfaceof an eyelid or adjacent to an eyelid or eye). In some cases, systems,devices, or methods described herein can be used to treat (e.g.,inhibit, disrupt, destroy, or remove) biofilms and/or pathogensassociated with (e.g., contained within) biofilms, which can beexceedingly difficult to disrupt, destroy, or remove from a subject. Inmany cases, antibiotics, creams, and ointments cannot penetratebiofilms. As described herein, applying an electric current to a targetarea comprising a biofilm can lead to the destruction (e.g.,vaporization) of a biofilm (and/or a pathogen within the biofilm, suchas a bacteria) at a target area. For instance, subjecting a biofilm to adirect current of low amperage, e.g., at a voltage of at least 6 voltsor more can destroy (e.g., vaporize) a biofilm. In some cases, a system,device, or method described herein can be used to treat or prevent acondition comprising or caused by debris, wherein the debris can includeone or more of a biofilm, bacteria, scurf, keratinization, dead cells,or secreted fluids, for example, at a target area. In some cases, atarget area of the present disclosure can comprise a skin surface. Insome cases, a target area can comprise a skin surface of an eyelid(e.g., an upper eyelid and/or a lower eyelid) or a margin thereof (e.g.,an upper eyelid margin or a lower eyelid margin), a skin surfaceadjacent to an eye or eyelid, or a gland, such as a skin gland. In somecases, a target area can comprise a surface of facial skin or a of askin of an extremity.

With reference to FIGS. 1A, 1B, 2A, and 2B and in accordance with someembodiments, devices 10 can be used to apply an electric current to,through, or across the skin of a subject. Application of the electriccurrent to, through, or across a target area of a subject (e.g., aportion of the skin of a subject, for instance a portion of the surfaceof the skin) may cause a debris present on, within, or proximal to thetarget area to be removed, vaporized, or otherwise disrupted. Examplesof debris can include, but are not limited to, biofilm, bacteria, scurf,keratinization, dead cells, and secreted fluids. In some cases, systems,methods, and devices 10 described herein can be used to apply electricalenergy to prevent or treat a treatable condition (e.g., an infection ordisease). Treatable conditions using the devices and method herein mayinclude, but are not limited to, blepharitis, acne, snoring, razorbumps, nose zits, dry eye, and skin conditions associated with aging(e.g., dry skin, roughened skin, keratoses, or inflammation). In someembodiments, the devices and methods herein can reduce signs of agingcaused by toxins produced by the bacteria/debris to be treated/removedby the devices and methods herein. In some embodiments, application ofelectrical energy (e.g., comprising an electrical signal) withinproximity of a nasal cavity can reduce snoring. Removal of inflammatorytoxins using the devices and methods herein may prevent the inflammatorytoxins from reaching the posterior pharynx by sniffing or andswallowing, reduce or eliminate the low-grade inflammation andsubsequent swelling associated with these toxins, which may therebytreat snoring conditions caused by such swelling and inflammation.

In some embodiments, a system or device 10 described herein includes oneor more electrodes 20, 22. In some cases, the one or more electrodes maybe placed in contact with (or adjacent to) a target area (e.g., a skinsurface) to apply a low voltage and low current electrical energythrough the skin. In some embodiments, the electrical current can bepassed through the epidermis and/or the dermis region(s) at or proximalto a target area (e.g., by contacting one or more skin surfaces with theone or more electrodes and passing electrical energy through theelectrodes). In some embodiments, electrical current can be passedthrough subcutaneous or hypodermis regions at or proximal to the targetarea (e.g., by contacting one or more skin surfaces with the one or moreelectrodes and passing electrical energy through the electrodes). Anelectrical current applied through the skin or to areas proximal to theskin surface at which the electrodes contact the skin may beadditionally referred to as an electrical signal, an electrical energy,an electric signal, an electric current, or an electric energy, in somecases.

In some embodiments, electrical energy applied to a target area (e.g.,by using one or more electrodes of a device described herein to pass theelectrical energy through the skin) can disrupt or vaporize debris orbiofilms. In some embodiments, disruption of debris can facilitateremoval of the debris. In some cases, removal of debris (e.g., from atarget area) can be facilitated by washing the target area with a washsolution or by wiping with a tissue or towel (e.g., after application ofelectrical energy to the target area by a device 10).

In many cases, electrical energy applied to a target area as describedherein (e.g., via one or more electrodes) can be supplied by a powersource and, optionally, regulated by a controller. In some embodiments,the voltage of the electrical energy applied can be about 0.1 V to about25 V. In some embodiments, the voltage of the electrical energy appliedto a target area (e.g., as supplied by the power source or as modulatedby the controller) can be about 0.1 V to about 0.5 V, about 0.1 V toabout 1 V, about 0.1 V to about 2 V, about 0.1 V to about 3 V, about 0.1V to about 5 V, about 0.1 V to about 10 V, about 0.1 V to about 12 V,about 0.1 V to about 15 V, about 0.1 V to about 20 V, about 0.1 V toabout 25 V, about 0.5 V to about 1 V, about 0.5 V to about 2 V, about0.5 V to about 3 V, about 0.5 V to about 5 V, about 0.5 V to about 10 V,about 0.5 V to about 12 V, about 0.5 V to about 15 V, about 0.5 V toabout 20 V, about 0.5 V to about 25 V, about 1 V to about 2 V, about 1 Vto about 3 V, about 1 V to about 5 V, about 1 V to about 10 V, about 1 Vto about 12 V, about 1 V to about 15 V, about 1 V to about 20 V, about 1V to about 25 V, about 2 V to about 3 V, about 2 V to about 5 V, about 2V to about 10 V, about 2 V to about 12 V, about 2 V to about 15 V, about2 V to about 20 V, about 2 V to about 25 V, about 3 V to about 5 V,about 3 V to about 10 V, about 3 V to about 12 V, about 3 V to about 15V, about 3 V to about 20 V, about 3 V to about 25 V, about 5 V to about10 V, about 5 V to about 12 V, about 5 V to about 15 V, about 5 V toabout 20 V, about 5 V to about 25 V, about 10 V to about 12 V, about 10V to about 15 V, about 10 V to about 20 V, about 10 V to about 25 V,about 12 V to about 15 V, about 12 V to about 20 V, about 12 V to about25 V, about 15 V to about 20 V, about 15 V to about 25 V, or about 20 Vto about 25 V. In some embodiments, the voltage of the electrical energyapplied can be about 0.1 V, about 0.5 V, about 1 V, about 2 V, about 3V, about 5 V, about 10 V, about 12 V, about 15 V, about 20 V, or about25 V. In some embodiments, the voltage of the electrical energy appliedcan be at least about 0.1 V, about 0.5 V, about 1 V, about 2 V, about 3V, about 5 V, about 10 V, about 12 V, about 15 V, or about 20 V. In someembodiments, the voltage of the electrical energy applied can be at mostabout 0.5 V, about 1 V, about 2 V, about 3 V, about 5 V, about 10 V,about 12 V, about 15 V, about 20 V, or about 25 V.

In some embodiments, the current of the electrical energy applied to atarget area (e.g., as supplied by a power supply or as modulated by acontroller) can be about 0.1 milliamps to about 4 milliamps. In someembodiments, the current of the electrical energy applied can be about0.1 milliamps to about 0.5 milliamps, about 0.1 milliamps to about 1milliamps, about 0.1 milliamps to about 1.5 milliamps, about 0.1milliamps to about 2 milliamps, about 0.1 milliamps to about 2.5milliamps, about 0.1 milliamps to about 3 milliamps, about 0.1 milliampsto about 3.5 milliamps, about 0.1 milliamps to about 4 milliamps, about0.5 milliamps to about 1 milliamps, about 0.5 milliamps to about 1.5milliamps, about 0.5 milliamps to about 2 milliamps, about 0.5 milliampsto about 2.5 milliamps, about 0.5 milliamps to about 3 milliamps, about0.5 milliamps to about 3.5 milliamps, about 0.5 milliamps to about 4milliamps, about 1 milliamps to about 1.5 milliamps, about 1 milliampsto about 2 milliamps, about 1 milliamps to about 2.5 milliamps, about 1milliamps to about 3 milliamps, about 1 milliamps to about 3.5milliamps, about 1 milliamps to about 4 milliamps, about 1.5 milliampsto about 2 milliamps, about 1.5 milliamps to about 2.5 milliamps, about1.5 milliamps to about 3 milliamps, about 1.5 milliamps to about 3.5milliamps, about 1.5 milliamps to about 4 milliamps, about 2 milliampsto about 2.5 milliamps, about 2 milliamps to about 3 milliamps, about 2milliamps to about 3.5 milliamps, about 2 milliamps to about 4milliamps, about 2.5 milliamps to about 3 milliamps, about 2.5 milliampsto about 3.5 milliamps, about 2.5 milliamps to about 4 milliamps, about3 milliamps to about 3.5 milliamps, about 3 milliamps to about 4milliamps, or about 3.5 milliamps to about 4 milliamps. In someembodiments, the current of the electrical energy applied can be about0.1 milliamps, about 0.5 milliamps, about 1 milliamps, about 1.5milliamps, about 2 milliamps, about 2.5 milliamps, about 3 milliamps,about 3.5 milliamps, or about 4 milliamps. In some embodiments, thecurrent of the electrical energy applied can be at least about 0.1milliamps, about 0.5 milliamps, about 1 milliamps, about 1.5 milliamps,about 2 milliamps, about 2.5 milliamps, about 3 milliamps, or about 3.5milliamps. In some embodiments, the current of the electrical energyapplied can be at most about 0.5 milliamps, about 1 milliamps, about 1.5milliamps, about 2 milliamps, about 2.5 milliamps, about 3 milliamps,about 3.5 milliamps, or about 4 milliamps.

In some embodiments, the current can be applied as direct current (DC).In some embodiments, the current can be applied as an alternatingcurrent (AC). In some embodiments, the current can be applied in asequence which includes alternating AC and DC currents, fluctuations incurrent amplitude, changing of AC current waveforms, and combinationsthereof.

In some embodiments, the device 10 for applying an electrical signal caninclude at least a first electrode 20 and a second electrode 22. In someembodiments, a surface of the electrodes 20,22 can be configured to beadhered to a skin surface. In some embodiments, the surface of theelectrodes which adhere to the skin surface can comprise a gel adhesive.The adhesive may allow for repeated placements of the electrodes ontothe skin surface. In some embodiments, a surface of the electrode 20, 22can be curved to generally correspond to the external curvature of askin surface. In some embodiments, the first and second electrodes canbe provided on separate surfaces, allowing a user to control the spacingbetween the electrodes. Each of the first and second electrodes 20, 22may have a width W and a length L. In some cases, an adhesive pad mayhave a width W and a length L. In some embodiments, each of the firstand second electrodes 20, 22 are the same size in area. In someembodiments, each of the first and second electrodes 20, 22 are adifferent size in area. In some embodiments, the one or more of theelectrodes or one or more of the adhesive pads are substantially squarehaving a width W approximately equal to the length L. In someembodiments, the one or more of the electrodes or one or more of theadhesive pads are substantially rectangular having a length L largerthan the width W. In some cases, one or more electrodes or one or moreadhesive pads are substantially circular, having a width W equal to adiameter of the electrode or pad. In some cases, one or more electrodesor one or more adhesive pads are substantially elliptical, having alength L equal to a major axis of the ellipse and a width W equal to aminor axis of the ellipse. In some cases, the width W of an electrodecan be 0.1 cm to 0.25 cm, 0.25 cm to 0.5 cm, 0.5 cm to 1.0 cm, 1.0 cm to1.5 cm, 1.5 cm to 2.0 cm, 2.0 cm to 2.5 cm, 2.5 cm to 3.0 cm, 3.0 cm to4.0 cm, 4.0 cm to 5.0 cm, or greater than 5.0 cm. In some cases, thelength L of an electrode can be 0.1 cm to 0.25 cm, 0.25 cm to 0.5 cm,0.5 cm to 1.0 cm, 1.0 cm to 1.5 cm, 1.5 cm to 2.0 cm, 2.0 cm to 2.5 cm,2.5 cm to 3.0 cm, 3.0 cm to 4.0 cm, 4.0 cm to 5.0 cm, or greater than5.0 cm. Electrodes and/or pads may be provided in various sizes andshapes (e.g., shaped to cover an eye or a portion thereof, such as aneyelid). Electrode or pad shapes may include square, circular,elliptical, oval, butterfly, curved and peanut shaped outlines. In somecases, an electrode or pad can be shaped to conform to a shape of atarget area or a body part of the subject (e.g., an eye).

In some embodiments, a voltage differential between the first and secondelectrodes may produce the electrical current which travels between theelectrodes and to areas of the skin proximal to the sites at which theelectrodes contact the skin surface. In some embodiments, a voltagedifferential between an electrode and the skin itself may produce theelectrical current which travels to areas of the skin proximal to thesites at which the electrodes contact the skin surface. In someembodiments, one of the first electrode or second electrodes 20, 22 mayfunction as a cathode and the other of the first electrode or secondelectrodes 20, 22 may function as an anode. In some embodiments, firstand second electrodes 20, 22 can be electrically coupled to a circuitthat may include a power supply 40 via one or more wire leads 50.

In some embodiments, the device can include a power supply 40, e.g.,wherein the power supply is configured to supply electrical energy tothe one or more electrodes. The device may also include hardware,software, or any combination thereof that may be used to control theelectrical energy being supplied to the electrodes. The hardware, suchas a controller 42, may include software and be electrically coupled tothe power supply 40 and the electrodes. Embodiments of the device mayalso include instructions supplied by a machine-readable medium, whichmay be read and executed by one or more processors. A machine-readablemedium may include any mechanism for storing or transmitting informationin a form readable by a machine (e.g., a computing device). For example,a machine-readable medium may include read only memory (ROM); randomaccess memory (RAM); magnetic disk storage media; optical storage media;flash memory devices; electrical optical, acoustical or other forms ofpropagated signals (e.g., carrier waves, infrared signals, digitalsignals, etc.), and others. Further software routines and instructionsmay be described herein as performing certain actions. However, itshould be appreciated that such descriptions are merely for convenienceand that such actions in fact result from computing devices, processors,controllers 42, or other devices executing the software, routines,instructions, etc.

In some embodiments, the controller can include a feedback circuit. Thefeedback circuit may be utilized to control parameters of the electricalsignal being produced by the electrodes. In some embodiments, electricaloutput at the electrode can be used as input into the feedback loop. Insome embodiments, voltage and/or current at one of the electrodes can beused as input into the feedback loop. The feedback input may be utilizedby the controller to determine parameters such as resistivity of theskin at which the electrical signal is applied, actual current appliedthrough the skin, and actual voltage applied through the skin. In someembodiments, the feedback loop can adjust the electrical signal tomaintain safe levels of voltage and current being supplied to the skinby the electrodes. In some embodiments, the feedback circuit ensuresthat can adjust the electrical signal such that is effective over anumber of variable, such as various skin types or ambient conditionssuch as humidity of the environment. In some embodiments, the feedbackcircuit can be a positive feedback circuit. In some embodiments, thefeedback circuit can be a negative feedback circuit.

In some embodiments, the device 10, may include a controller 42comprising a user interface that includes an input system and a displaysystem. The input system allows the user to adjust the operation of thedevice 10, and, in some embodiments, interact with the controller 42 tocontrol the device. For example, the user interface may allow the userto activate the supply of electrical energy to the electrodes 20, 22, toincrease or decrease the electrical energy being supplied to theelectrodes 20, 22, increase or decrease the duration of treatment, andcombinations thereof.

With reference to FIG. 2A and FIG. 2B, the input system may include atleast one of a button 46, a dial 48, a trigger, a switch, a touchscreen, and/or other input devices as are known in the electrical arts.A display system may convey information to the user with respect to thestatus of the device. In some embodiments, the display may include oneor more lights 52 such as light emitting diodes, an LCD display 47,gauges, or other types of displays as are known in the art. For example,the controller 42 may include one or more lights 52 to indicate thepowered on status of the device, indicate the level of energy remainingin the power supply, such as in a battery, or if the electrodes aremaking sufficient contact with the skin of the subject undergoingtreatment.

In some embodiments, as depicted by FIG. 2A and FIG. 2B, the controller42, power supply 40, and user interface (e.g., lights 52 and buttons 46)are contained in a housing. It will be appreciated that the controller,power supply, user interface, and other components may be in one or morehousings and the one or more housings. A housing with one or morecomponents may be a base unit that can be located some distance awayfrom the subject but that is also electrically coupled to the skincontacting portion by a flexible member, such as an electric cable.

In some embodiments, the controller comprises a plurality of electrodeoutputs 25. In some embodiments, each output 25 is labeled as a positiveor negative output. In some embodiments, each output is labeled as acathode or anode output. The outputs 25 may be colored corresponding tothe electric polarity (i.e. red for positive and black for negative orvice versa). In some embodiments, the polarity of the output 25 isselected using the controller.

As depicted in FIGS. 2B, 3A, 3D, and 3E, one or more electrodes 20, 22may be included on a single pad 23. In some embodiments, the pad 23 canbe configured to be placed on a specific skin surface. In someembodiments, wherein the device can be configured to treat a snoringcondition, the pad 23 can be shaped similar to a nasal strip orbutterfly strip. In some embodiments, the pad 23 can be adhered to anose of a user, such that the first electrode 20 is placed on a firstside of the nose, and the second electrode 22 can be placed on theopposite of the nose, with the narrow region being placed across thebridge of the nose.

In some embodiments, providing one or more electrodes on a single padfixes the distance between the electrodes. Fixing the distance between afirst electrode 20 and a second electrode 22 may reduce chances ofmisplacement and improve the efficacy of the device. In someembodiments, each electrode 20, 22 of the pad can be connected to aseparate lead wire 50. In some embodiments, the lead wires 50 can beconnected to outputs of a controller (e.g. outputs 25 of controller 42as depicted by FIG. 2A and FIG. 2B).

In some embodiments, the electrode pads can be configured to surroundthe mouth to vaporize intra-oral biofilm. In some embodiments, theelectrode pads can be configured to adhere to the eyelids to vaporizebiofilm along the eyelid margins. As depicted in FIG. 3C and FIG. 3E,electrode pads to be placed on the eyelids may comprise two teardrop oralmond-shaped electrodes 20,22 or electrode pads 23.

Secondary benefits of electrical therapy applied to the skin may includereduction of blepharitis (inflammation of the eyelids caused byvirulence factors), acne inside the nose, and acne on the face.Reduction of acne on the face may be enhanced by using pads on the cheekareas. Electrical therapy may reduce the signs of aging by reducing theamount of virulence factors which are swallowed on a daily basis.

In some embodiments, a solution may be applied to the skin to reduce anelectrical resistivity or impedance of the skin. In some embodiments,the solution is an electrolyte solution. In some embodiments, thesolution is applied to the skin to improve the disruption of debris bythe electrical energy.

Pads

A system, device, or method described herein can comprise one or morepads 23. A pad 23 described herein can be configured to contact a targetarea (e.g., an affected skin surface) or a region adjacent to a targetarea. A pad 23 (e.g., an adhesive pad) can comprise an adhesive or otheragent for placing the pad 23 or component thereof (e.g., one or moreelectrodes of the pad 23) in contact with or in proximity to a targetarea (e.g., a skin surface of a subject). In some cases, an adhesive canbe a gel, a glue, or a viscous fluid. In some cases, an adhesive can beelectrolytic. For example, an adhesive can facilitate transmission ofelectrical energy to a target area, in some cases.

In many cases, a pad 23 can comprise one or more electrodes, forexample, wherein the one or more electrodes are connected to a powersupply and/or a controller (e.g., via one or more wires). An electrodeof a pad 23 can be used to deliver electrical energy to a target area(e.g., a skin surface of a subject). In some cases, a pad 23 cancomprise an electrically non-conductive material coupled to one or moreelectrodes. In some cases, a pad 23 can be coupled to a plurality ofelectrodes. In some cases, a pad 23 can be coupled to an anode electrodeand a cathode electrode. In some cases, a pad 23 can be coupled to ananode electrode and a second pad 23 can be coupled to a cathodeelectrode (e.g., wherein the anode electrode and cathode electrode areelectrically connected to a power supply and/or a controller of asystem, devices, or method described herein).

In many cases, a system, device, or method described herein comprises aplurality of pads 23. For instance, a system, device, or methoddescribed herein can comprise a first pad 23 for contacting a firsttarget region (e.g., a target region on a first eye or eyelid of asubject) and a second pad 23 for contacting a second target region(e.g., wherein the second target region is on or adjacent to a secondeye or eyelid of the subject).

In some cases, a pad 23 can be applied to a target area of a subject inneed of treatment. In some cases, a first pad 23 can be coupled to(e.g., adhered to) a first region of a target area and a second pad 23coupled to a second region of the target area. In some cases, a firstpad 23 can be coupled to (e.g., adhered to) to a first region adjacentto a target area and a second pad 23 can be coupled to a second regionadjacent to the target area.

Controllers

A system, device, or method described herein can comprise a controller.A controller can be connected to a power supply (e.g., via one or morewires) and/or to one or more electrodes (e.g., one or more electrodes ofone or more pads 23 described herein). A controller can comprise aprocessor, a memory, and/or a user interface. A memory (e.g., anon-transitory memory) of a controller can comprise instructions that,when executed, can cause the processor to perform one or more steps of amethod described herein. For instance, a controller can be configured tomodulate an electrical signal from a power supply. In some cases, acontroller can be configured to modulate an amplitude (e.g., a currentamplitude or a voltage amplitude) of electrical energy (e.g., providedby a power supply), which may be transmitted to one or more electrodes(e.g., via wires 50) for application to a target area. In some cases, acontroller can be configured to modulate a frequency (e.g., of a currentor voltage) of electrical energy (e.g., provided by a power supply),which may be transmitted to one or more electrodes (e.g., via wires 50)for application to a target area. In some cases, electrical energymodulated by a controller can comprise an electrical signal (e.g.,comprising a waveform). In some cases, applying electrical energy in theform of an electrical signal (e.g., comprising a waveform) to a targetarea (e.g., via one or more electrodes) can improve prevention ortreatment of a target area, as described herein, in some embodiments.

In many cases, electrical energy can be applied (e.g., in the form of avoltage drop between two electrodes on separate adhesive pads or in theform of a voltage drop across two electrodes in a single adhesive pad)to a target area (e.g., a skin surface of a subject) without thedelivery of another form of energy to the target area. For example,delivery of electrical energy to a target area using systems, devices,and methods described herein can be sufficient for treating orpreventing a condition described herein (e.g., without application ofanother form of energy to the target area during the practice of thesystem, device, or method). In some embodiments, ultrasonic energy canbe applied without the application of any other form of energy todisrupt debris. In some cases, electrical energy can be administered toa target area (e.g., a skin surface of an eye) using a system, device,or method described herein while another form of energy (e.g.,ultrasonic energy) may be applied to the target region (e.g., via anadhesive pad described herein). In some cases, a treatment of a subjectcan comprise applying electrical energy and another form of energy tothe target area at different times. In some cases, a treatment of asubject can comprise applying only electrical energy to the target area.In some cases, electrical energy and the other form of energy, such asultrasonic energy, may be applied in an alternating manner, or one ofthese forms of energy may be applied first and the other form of energymay be applied second. This alternating pattern may be repeated. In anembodiment, the other form of energy, such as ultrasonic energy, can beapplied first and the electrical energy can be applied second. Inanother embodiment, the electrical energy can be applied first and theother form of energy, such as ultrasonic energy, can be applied second.The electrical energy can be applied for a duration and at a frequencysufficient to disrupt debris (e.g., biofilm) on the eyelid, and inparticular debris (e.g., biofilm) on the eyelid margin.

FIG. 4 depicts a graph 200 that shows an exemplary monophasic waveform202 which may be used to provide electrical energy to an eye contactingportion (e.g., comprising a pad 23 and/or one or more electrodes 20, 22)of device 10. The monophasic waveform 202 may include a plurality ofpulses (e.g., an initial pulse 204 and subsequent pulse 206) that repeatover a cycle time 208 and which can be used to electrolytically disruptdebris on an eyelid margin. Each pulse 204, 206 may have a pulseduration 210 and an interpulse duration 212 that collectively define thecycle time 208 of monophasic waveform 202. Each pulse 204, 206 may havea relatively short rise time 214, 216 during which the amplitude of themonophasic waveform 202 rises from an initial baseline amplitude a0(e.g., zero volts or amps) to a peak 218, 220 having a peak amplitudea1, and fall time 222, 224 during which the amplitude of the monophasicwaveform 202 falls back toward the baseline amplitude a0, e.g., bydecaying at a generally exponential rate.

Prior to time t0, the monophasic waveform 202 may be at the initialbaseline amplitude a0. At the beginning of the cycle time 208, theamplitude of the monophasic waveform may begin rising and reach theinitial peak 218 in a relatively short period of time, e.g., 1 μs. Afterreaching the initial peak 218, the amplitude of the monophasic waveform202 may drop back toward the baseline amplitude a0 over a period oftime. The drop in the amplitude may be exponential in nature as theelectrical energy dissipates into the patient. The period between peaks218, 220 may be selected to allow the amplitude of the monophasicwaveform to essentially return to the baseline amplitude a0 beforegenerating subsequent peak 220. At time t1, the amplitude of themonophasic waveform 202 may begin to rise to subsequent peak 220, whichmay have the same amplitude a1 as the initial peak 218. The amplitude ofthe monophasic waveform may then drop back toward the baseline amplitudea0 over a period of time in similar manner as described for the initialpeak 218. After the final pulse of the plurality of pulses, themonophasic waveform 202 may remain at baseline amplitude a0 for theremainder of cycle time 208.

The amplitude of the monophasic waveform 202 may be characterized usingcurrent or voltage so that the baseline amplitude a0 is zero volts oramps. For peaks 218, 220 characterized by voltage, the peak amplitude a1may be approximately 350 V. For peaks 218, 220 characterized by current,the peak amplitude a1 may be approximately 700 mA. An exemplarymonophasic waveform 202 may have a cycle time 208 of approximately 10 msand a pulse duration 210 of approximately 0.2 ms.

FIG. 5 depicts a graph 230 that shows an exemplary biphasic waveform 232that may be used to provide electrical energy to the eye contactingportion (e.g., comprising an adhesive pad and/or one or more electrodes)of device 10. The biphasic waveform 232 may be asymmetric, and mayinclude a pulse 234 that repeats over a cycle time 236 and which can beused to electrolytically disrupt debris on an eyelid margin. Each pulse234 may include a positive phase 238, a negative phase 240, and a pulseduration 242. The pulse duration 242 and an interpulse duration 244 maycollectively define the cycle time 236 of biphasic waveform 232.

The positive phase 238 of pulse 234 may have a relatively short risetime 246 (e.g., 1 microseconds (μS) during which the amplitude of thebiphasic waveform 232 rises from the initial baseline amplitude a0 to apositive peak amplitude a3, and relatively short fall time 248 duringwhich the amplitude of the biphasic waveform 232 falls toward a negativepeak amplitude a4. In an embodiment of the invention, the positive peakamplitude a3 may have about the same magnitude as the negative peakamplitude a4. The positive phase 238 may comprise a portion (e.g., abouta third) of the pulse 234 during which the amplitude of biphasicwaveform 232 is held at the positive peak amplitude a3. During thenegative phase 240 of pulse 234, the amplitude of the biphasic waveform232 may decay or be driven toward the baseline amplitude a0 at agenerally linear rate from the negative peak amplitude a4 back towardthe baseline amplitude a0 over the remaining portion of the pulseduration 242.

The amplitude of the biphasic waveform 232 may also be characterizedusing current or voltage. In cases where the biphasic waveform 232 ischaracterized by voltage, the peak amplitude a5 may be in a range ofapproximately 0 to +50V, and the peak amplitude a4 may be in a range ofapproximately 0 to −50V. In cases where the biphasic waveform 232 ischaracterized by current, the peak amplitude a5 may be in a range ofapproximately 0 to +100 mA, and the peak amplitude a4 may be in a rangeof approximately 0 to −100 mA. An exemplary biphasic waveform 232 mayhave a pulse duration 242 in a range of approximately 50 to 300 μs, andmay be user adjustable in increments, e.g., 10 μs increments. Theexemplary biphasic waveform may further include a cycle time 236 in arange of approximately 6.67 to 500 ms, yielding a frequency of 2-150 Hz,and may be adjustable in increments of frequency, e.g., 1 Hz increments.

FIG. 6 depicts a graph 250 that shows an exemplary triphasic waveform252 that may be used to provide electrical energy to the eye contactingportion (e.g., comprising a pad and/or one or more electrodes) of device10. The triphasic waveform 252 may include a pulse 254 that repeats overa cycle time 256 and which can be used to electrolytically disruptdebris on an eyelid margin. Each pulse 254 may include two positivephases 258, 260, a negative phase 262, and a pulse duration 264. Thepulse duration 264 and an interpulse duration 266 may collectivelydefine the cycle time 256 of triphasic waveform 252.

The initial positive phase 258 may have a peak 268 that predominatesover peak 270 of subsequent positive phase 260 and over peak 272 ofnegative phase 262. That is, the amplitude a5 of peak 268 may be greaterthan the amplitudes a6, a7 of the subsequent peaks 270, 272. Each of thephases 258, 260, 262 may have a generally sinusoidal shape with peakamplitudes a5, a6, a7 that follow a generally exponential decay rate ascompared to the preceding peaks 268, 270, 272.

Prior to time t0, the triphasic waveform 252 may initially be at thebaseline amplitude a0. At the beginning of the cycle time 256, theamplitude of the triphasic waveform 252 may rise to positive peak 268following a generally sinusoidal curve. The amplitude of the triphasicwaveform 252 may then drop below the baseline amplitude a0 over a periodof time following a generally sinusoidal curve to reach negative peak272 between zero-crossing times t3 and t4. The amplitude of thetriphasic waveform 252 may then begin to rise above the baselineamplitude a0 over a period of time following a generally sinusoidalcurve to reach positive peak 270 between zero-crossing times time to andt5. Each peak 270, 272 may have a reduced magnitude in comparison to themagnitude of the immediately preceding peak 268, 270. After reachingpeak 270, the amplitude of the triphasic waveform 252 may drop towardthe baseline amplitude a0 over a period of time and remain there for theremainder of cycle time 256.

FIG. 7 depicts an exemplary controller 42 in accordance with anembodiment of the invention. The controller 42 may include a processor300, a memory 302, an input/output (I/O) interface 304, and a userinterface 306. The processor 300 may include one or more devicesselected from microprocessors, micro-controllers, digital signalprocessors, microcomputers, central processing units, field programmablegate arrays, programmable logic devices, state machines, logic circuits,analog circuits, digital circuits, or any other devices that manipulatesignals (analog or digital) based on operational instructions that arestored in the memory 302. Memory 302 may be a single memory device or aplurality of memory devices including but not limited to read-onlymemory (ROM), random access memory (RAM), volatile memory, non-volatilememory, static random access memory (SRAM), dynamic random access memory(DRAM), flash memory, cache memory, or any other device capable ofstoring digital information. Memory 302 may also include a mass storagedevice (not shown) such as a hard drive, optical drive, tape drive,non-volatile solid state device or any other device capable of storingdigital information.

Processor 300 may operate under the control of an operating system 308that resides in memory 302. The operating system 308 may managecontroller resources so that computer program code embodied as one ormore computer software applications, such as a controller application310 residing in memory 302 may have instructions executed by theprocessor 300. In an alternative embodiment, the processor 300 mayexecute the controller application 310 directly, in which case theoperating system 308 may be omitted. One or more data structures 312 mayalso reside in memory 302, and may be used by the processor 300,operating system 308, and/or controller application 310 to store data.

The I/O interface 304 may operatively couple the processor 300 to othercomponents of embodiments of the invention, such as electrodes 20, 20 a,20 b, 20 c, 22, 22 a, 22 b, 22 c, 24, 24 a, 26, 26 a, pump 100, and/orvacuum pump 101. The I/O interface 304 may include signal processingcircuits that condition incoming and outgoing signals so that thesignals are compatible with both the processor 300 and the components towhich the processor 300 is coupled. To this end, the I/O interface 304may include analog-to-digital (A/D) and/or digital-to-analog (D/A)converters, voltage level and/or frequency shifting circuits, opticalisolation and/or driver circuits, and/or any other analog or digitalcircuitry suitable for coupling the processor 300 to the othercomponents of embodiments of the invention.

The user interface 306 may be operatively coupled to the processor 300of controller 42 in a known manner to allow a system operator tointeract with the controller 42. The user interface 306 may include adisplay such as a video monitor, alphanumeric displays, a touch screen,a speaker, and any other suitable audio and visual indicators capable ofproviding information to the system operator. User interface 306 mayalso include input devices and controls such as an alphanumerickeyboard, a pointing device, keypads, pushbuttons, control knobs,microphones, etc., capable of accepting commands or input from theoperator and transmitting the entered input to the processor 300. Inthis way, user interface 306 may enable manual initiation or selectionof system functions, for example, during system set-up, calibration, andchemical loading.

Applications

Among the causes thought to play a role in many chronic conditions ofthe skin and/or eyes is the formation of biofilms in the environment ofthe eye. Such causes may play a role in the formation and/or developmentof teenage acne and Acne Rosacea. Bacteria that produce biofilms, mainlyStaph aureus and Staph epidermidis, are still present in vast numbers.Structures of the body can retain moisture, which can provide a nichefor growth of bacteria, including those that produce biofilms such asStaph aureus and Staph epidermidis, within the skin (e.g., various sweatand sebaceous glands). During adolescence, when the hormonal balancesare changing, sweat and sebum may be overproduced and provide a verymoist environment. This moist environment may allow for bacteria toproduce biofilm. It is highly likely that during this time ofadolescence thin biofilms develop on the face, since this is the area ofmost glandular activity. The biofilm may slowly creep into the glandsand within the biofilm, bacteria may begin producing toxins. Thesetoxins may lead to inflammation within the glands, known as teenageacne. As the hormones stabilize, normal rapid cellular turnover of youthtends to eliminate the glands with biofilm, and complexion returns tonormal. Systems, devices, and methods described herein can be useful intreating or preventing pathogens such as bacteria and/or biofilms frompersisting in or on a subject's skin.

The overall production of virulence factors on all warm moist surfacesabove the neck may cause one or more of several different maladies whichcan be treated or prevented by the systems, devices, and methodsdescribed herein, not just acne. The disease or condition to be treatedmay depend on where the electrode pads are placed. The biofilms in allof these locations eventually send the virulence factors they produce tothe posterior pharynx area via swallowing or sniffing. Virulence factorsmay travel through the nasolacrimal duct to the posterior sinuses and tothe posterior pharynx by swallowing. The toxins may contact theposterior pharynx where they induce a small amount of inflammation whichcauses slight edema to occur, resulting in snoring. In some embodiments,the electrode pads are configured to be placed on the nose to vaporizebiofilm within the nasal and sinus cavities and treat a snoringcondition. As depicted in FIG. 3B and FIG. 3D, electrode pads 20, 22 tobe placed on the nose may comprise two round or substantially circularelectrode pads. In some embodiments, the electrode pads are placed onopposite sides of the nose. The electrode pads may comprise variousshapes and may vaporize biofilm, thereby reducing the virulence factors,decreasing toxins which are passed to the posterior pharynx. Even theslightest edema within the posterior pharynx can cause a closeapproximation of the walls of this area causing air movement to flutterthese walls open and closed causing the sound of snoring.

In older adults the mechanism may be slightly different. Accumulation ofbiofilm within the facial glands occurs not because of a burst ofhormonal activity, but because of age. The bacteria have more years tofinally gain a microscopic foothold in the facial glands, and veryslowly the biofilm may begin to accumulate. It can be much slower thanin the mouth or on the eyelids because there is much less moisture,however, once biofilm captures an area it seldom gives it up. With theslower cellular turnover of adults, and the affected glands acting asreservoirs for further biofilm advancement and accumulation,inflammation on the face may show up along with telangiectatic vesselscausing a condition referred to as Acne rosacea. This disease has provenextremely hard to treat, since the biofilm cannot be removed. Compoundssuch as retinol can increase cell turnover, and sometimes improve signsand symptoms, but any relief is typically short lived if not accompaniedby additional therapy capable of removing the biofilm, such as the useof a system, device, or method described herein (e.g., comprisingapplication of electrical energy to an affected target area).

Unless defined otherwise, all terms of art, notations and othertechnical and scientific terms or terminology used herein are intendedto have the same meaning as is commonly understood by one of ordinaryskill in the art to which the claimed subject matter pertains. In somecases, terms with commonly understood meanings are defined herein forclarity and/or for ready reference, and the inclusion of suchdefinitions herein should not necessarily be construed to represent asubstantial difference over what is generally understood in the art.

Throughout this application, various embodiments may be presented in arange format. It should be understood that the description in rangeformat is merely for convenience and brevity and should not be construedas an inflexible limitation on the scope of the disclosure. Accordingly,the description of a range should be considered to have specificallydisclosed all the possible subranges as well as individual numericalvalues within that range. For example, description of a range such asfrom 1 to 6 should be considered to have specifically disclosedsubranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4,from 2 to 6, from 3 to 6 etc., as well as individual numbers within thatrange, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of thebreadth of the range.

As used in the specification and claims, the singular forms “a”, “an”and “the” include plural references unless the context clearly dictatesotherwise. For example, the term “a sample” includes a plurality ofsamples, including mixtures thereof.

The terms “determining,” “measuring,” “evaluating,” “assessing,”“assaying,” and “analyzing” are often used interchangeably herein torefer to forms of measurement. The terms include determining if anelement is present or not (for example, detection). These terms caninclude quantitative, qualitative or quantitative and qualitativedeterminations. Assessing can be relative or absolute. “Detecting thepresence of” can include determining the amount of something present inaddition to determining whether it is present or absent depending on thecontext.

The terms “subject,” “individual,” or “patient” are often usedinterchangeably herein. A “subject” can be a biological entitycontaining expressed genetic materials. The biological entity can be aplant, animal, or microorganism, including, for example, bacteria,viruses, fungi, and protozoa. The subject can be tissues, cells andtheir progeny of a biological entity obtained in vivo or cultured invitro. The subject can be a mammal. The mammal can be a human. Thesubject may be diagnosed or suspected of being at high risk for adisease. In some cases, the subject is not necessarily diagnosed orsuspected of being at high risk for the disease.

As used herein, the term “about” a number refers to that number plus orminus 10% of that number. The term “about” a range refers to that rangeminus 10% of its lowest value and plus 10% of its greatest value.

As used herein, the terms “treatment” or “treating” are used inreference to a pharmaceutical or other intervention regimen forobtaining beneficial or desired results in the recipient. Beneficial ordesired results include but are not limited to a therapeutic benefitand/or a prophylactic benefit. A therapeutic benefit may refer toeradication or amelioration of symptoms or of an underlying disorderbeing treated. Also, a therapeutic benefit can be achieved with theeradication or amelioration of one or more of the physiological symptomsassociated with the underlying disorder such that an improvement isobserved in the subject, notwithstanding that the subject may still beafflicted with the underlying disorder. A prophylactic effect includesdelaying, preventing, or eliminating the appearance of a disease orcondition, delaying or eliminating the onset of symptoms of a disease orcondition, slowing, halting, or reversing the progression of a diseaseor condition, or any combination thereof. For prophylactic benefit, asubject at risk of developing a particular disease, or to a subjectreporting one or more of the physiological symptoms of a disease mayundergo treatment, even though a diagnosis of this disease may not havebeen made.

The section headings used herein are for organizational purposes onlyand are not to be construed as limiting the subject matter described.

The invention claimed is:
 1. A device for providing an electrical therapy to a skin of a subject comprising: one or more electrode pads comprising a transmission surface, the one or more electrode pads comprising a first electrode and a second electrode; a power supply in electrical communication with the first and second electrodes; and a controller to regulate voltage, current, or both of an electrical signal supplied the first and second electrodes by the power supply, wherein the one or more electrode pads are shaped to conform to the skin of an eye, eyelid, eyelid margin, nose, or mouth of the subject, wherein the device is configured to generate a plurality of pulses, and wherein the device is configured to vaporize a biofilm.
 2. The device of claim 1, wherein the controller supplies a first voltage to the first electrode, and a second voltage to the second electrode, thereby creating a voltage potential between the first electrode and the second electrode.
 3. The device of claim 2, wherein the first and second electrode are configured to contact a skin surface to generate an electric current through the skin.
 4. The device of claim 1, wherein the vaporizing a biofilm is via the electric current through the skin.
 5. The device of claim 3, wherein the controller is configured to measure an impedance of the skin based on a measured impedance.
 6. The device of claim 1, wherein the voltage of the electrical signal is about 0.1 V to about 20 V.
 7. The device of claim 1, wherein the current of the electrical signal is less than about 5 milliamps (mA).
 8. The device of claim 1, further comprising a housing and a wire lead, wherein the power supply and the controller are disposed within the housing, and wherein the wire lead connects the power supply and controller to the transmission surface.
 9. The device of claim 1, wherein the current of the electrical signal is an alternating current signal.
 10. The device of claim 1, wherein the current of the electrical signal is a direct current signal.
 11. The device of claim 1, wherein the electrical therapy configured to treat acne, snoring, dry eye, premature aging, or a combination thereof. 